Leptin elimination in hyperleptinaemic peritoneal dialysis patients

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little residual renal function and many have grossly of Pediatrics, Washington University ... toneal dialysis (CAPD) treatment for ESRD gave written. Plasma leptin ...
Nephrol Dial Transplant (1999) 14: 732–737

Nephrology Dialysis Transplantation

Original Article

Leptin elimination in hyperleptinaemic peritoneal dialysis patients Michael Landt1, Curtis A. Parvin2, Samuel Dagogo-Jack2, Barbara Bryant2 and Daniel W. Coyne2 Departments of 1Pediatrics and 2Medicine, Washington University School of Medicine, St. Louis, MO, USA

Abstract Background. Elevated plasma concentrations of leptin, a hormone thought to regulate body composition by influencing food intake/metabolic rate, are prevalent in renal failure patients. The mechanism for these increases is not known, but evidence suggests that simple accumulation due to decreased elimination is insufficient explanation. Methods. We studied the incidence of hyperleptinaemia in 28 end-stage renal disease patients treated with continuous ambulatory peritoneal dialysis (CAPD), compared with body-mass-index-and sex-matched controls. Results were separated by gender because women have higher leptin concentrations than men. Excretion of leptin and other substances in dialysis fluid was also studied. Results. Hyperleptinaemia was prevalent in women CAPD subjects, but not in men. Plasma leptin concentrations correlated strongly with the daily excretion of leptin in dialysis fluid. Clearance of leptin in dialysis fluid was greater in men than women CAPD subjects. Single regression analysis found that fasting insulin, glucose content of dialysis fluid, plasma albumin, C-reactive protein, erythropoietin dose, urinary creatinine clearance and plasma b 2 microglobulin were not determinants of plasma leptin concentrations. Stepwise forward multiple regression, examining the dependence of plasma leptin on body mass index, renal creatinine clearance, plasma albumin, daily dialysis fluid glucose load, daily leptin in dialysis fluid, erythropoietin dose and plasma C-reactive protein found only erythropoietin dose as a consistent negative predictor of plasma leptin concentrations. Conclusions. The results suggest that hyperleptinaemia of CAPD was due to predisposing loss of renal elimination capacity combined with increased production due to obesity (more prevalent in women subjects of this study) and potentially female gender.

Correspondence and offprint requests to: Dr M. Landt, Department of Pediatrics, Washington University School of Medicine, One Children’s Place, St. Louis, MO 63110, USA.

Introduction Leptin, the hormone produced by adipose tissue and thought to be involved in regulating body composition by influencing food intake/metabolic rate [1–4], has been shown in several studies to be elevated in the plasma of renal failure patients [5–10], particularly in end-stage renal disease (ESRD) treated with haemodialysis [5–9] and peritoneal dialysis [7–10]. Although plasma leptin concentrations vary directly with percent body fat in normal lean and obese subjects, such that obese subjects have very high leptin concentrations [11,12], the elevations seen in many renal failure patients are much greater than predicted by their adiposity. The kidney appears to be the principal site of elimination of circulating leptin in healthy subjects and in rats, perhaps by a mechanism involving cellular uptake [6,13–16 ]. Elevated leptin concentrations in renal failure patients cannot be fully explained by simple accumulation due to decreased elimination; the degree of elevation does not generally correlate with indices of renal impairment and many patients with severe renal disease (i.e. most hemodialysis patients) have plasma leptin concentrations that are appropriate for their adiposity [5,6 ]. An alternative explanation is that leptin production is increased, perhaps as a secondary effect of underlying disease or in response to uraemia. Recent studies have reported a significant correlation of plasma leptin with fasting insulin concentrations [17] and with C-reactive protein [8] in renal failure patients. Chronic elevated insulin concentrations have been shown to increase plasma leptin concentrations in normal subjects [18–20]. Administration of endotoxin or tumour necrosis factor ( TNF )-a to rodents produces a strong elevation of plasma leptin, along with decreased food intake [21,22]. Elevated plasma leptin concentrations seen in many renal failure patients could result from increased production in response to accumulated insulin or to increased levels of cytokines, which might be reflected as elevated C-reactive protein [8,17]. In an effort to explain the hyperleptinaemia of renal failure, we have studied potential correlates of leptin metabolism and particularly leptin elimination by dialysis in peritoneal dialysis patients. These patients have little residual renal function and many have grossly elevated plasma leptin levels.

© 1999 European Renal Association–European Dialysis and Transplant Association

Leptin elimination by peritoneal dialysis

Materials and methods


2.0 (Jandel Corp., San Rafael, CA, USA). Statistical significance was regarded as P-values

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